CN104334226B - Implantable solid liquid preparation delivery apparatus, preparation and application method - Google Patents

Implantable solid liquid preparation delivery apparatus, preparation and application method Download PDF

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Publication number
CN104334226B
CN104334226B CN201280067186.1A CN201280067186A CN104334226B CN 104334226 B CN104334226 B CN 104334226B CN 201280067186 A CN201280067186 A CN 201280067186A CN 104334226 B CN104334226 B CN 104334226B
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China
Prior art keywords
reservoir
liquid
delivery
mixing chamber
medicine
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Expired - Fee Related
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CN201280067186.1A
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Chinese (zh)
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CN104334226A (en
Inventor
米尔·伊姆兰
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Incube Laboratories LLC
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Incube Laboratories LLC
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/1407—Infusion of two or more substances
    • A61M5/1409—Infusion of two or more substances in series, e.g. first substance passing through container holding second substance, e.g. reconstitution systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M39/00—Tubes, tube connectors, tube couplings, valves, access sites or the like, specially adapted for medical use
    • A61M39/02—Access sites
    • A61M39/0208—Subcutaneous access sites for injecting or removing fluids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142—Pressure infusion, e.g. using pumps
    • A61M5/14244—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body
    • A61M5/14276—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body specially adapted for implantation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/168—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body
    • A61M5/16804—Flow controllers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M39/00—Tubes, tube connectors, tube couplings, valves, access sites or the like, specially adapted for medical use
    • A61M39/02—Access sites
    • A61M39/0208—Subcutaneous access sites for injecting or removing fluids
    • A61M2039/0238—Subcutaneous access sites for injecting or removing fluids having means for locating the implanted device to insure proper injection, e.g. radio-emitter, protuberances, radio-opaque markers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M39/00—Tubes, tube connectors, tube couplings, valves, access sites or the like, specially adapted for medical use
    • A61M39/02—Access sites
    • A61M39/0247—Semi-permanent or permanent transcutaneous or percutaneous access sites to the inside of the body
    • A61M2039/0261—Means for anchoring port to the body, or ports having a special shape or being made of a specific material to allow easy implantation/integration in the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M39/00—Tubes, tube connectors, tube couplings, valves, access sites or the like, specially adapted for medical use
    • A61M39/02—Access sites
    • A61M39/0247—Semi-permanent or permanent transcutaneous or percutaneous access sites to the inside of the body
    • A61M2039/0282—Semi-permanent or permanent transcutaneous or percutaneous access sites to the inside of the body with implanted tubes connected to the port
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M39/00—Tubes, tube connectors, tube couplings, valves, access sites or the like, specially adapted for medical use
    • A61M39/02—Access sites
    • A61M39/0247—Semi-permanent or permanent transcutaneous or percutaneous access sites to the inside of the body
    • A61M2039/0294—Semi-permanent or permanent transcutaneous or percutaneous access sites to the inside of the body having a specific shape matching the shape of a tool to be inserted therein, e.g. for easy introduction, for sealing purposes, guide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/02—General characteristics of the apparatus characterised by a particular materials
    • A61M2205/0244—Micromachined materials, e.g. made from silicon wafers, microelectromechanical systems [MEMS] or comprising nanotechnology
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/50—General characteristics of the apparatus with microprocessors or computers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/168—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body
    • A61M5/16804—Flow controllers
    • A61M5/16827—Flow controllers controlling delivery of multiple fluids, e.g. sequencing, mixing or via separate flow-paths

Abstract

Embodiments of the present invention provide the apparatus and method for delivering liquid form medicine in vivo, wherein the medicine is stored in solid form, and are then mixed with liquid in internal device is implanted in.One implementation method provides the embedded type device for delivering in vivo medicine, and the device includes housing, and the housing includes reservoir, solid form drug-reservoir (SSM) and pump.SSM elements are added to reservoir to form the drug solution comprising at least one medicament together with liquid.Then drug solution is delivered to site of delivery using being used to solution to be pumped to the pumping installations of site of delivery through delivery members such as conduits from reservoir.Embodiments of the present invention are for the long-term treatment medical conditions in the case where topical administration is taken without patient being particularly useful to patient delivery's medicine.

Description

Implantable solid-liquid preparation delivery apparatus, preparation and application method
Cross-Reference to Related Applications
Submitted to this application claims on November 22nd, 2011, entitled " Implantable Solid-Liquid Drug The U.S. Provisional Patent Application the 61/th of Delivery Apparatus, Formulations and Methods of Use " The priority of 629, No. 666, the temporary patent application is for all purposes and by reference to being integrally incorporated in this.
Background technology
Invention field.Embodiments of the present invention are related to agent delivery device and its application method.More specifically, of the invention The implementation method implanted agent delivery device that is related to for delivering medicament and other therapeutic agents.
Current trend in many medical treatments be need to particular target site delivery medicament with avoid adverse reaction and/ Or to the toxicity (for example, in the case of the chemotherapeutics for treating cancer) of its hetero-organization, and precisely control delivering Timing and amount to the medicament at the position.In many cases, this may need to use implanted Teat pipette.However, due to current The size and power requirement of available pump, they are not suitable for all of medical applications, particularly non-for may wherein need Often accurately control the drug delivery of drug dose.In addition, current device may be due to limited reservoir size and/or limited The medicament pot-life and need frequently to supplement medicament.Accordingly, there exist to the improved implanted medicine for internal drug delivery The demand of agent delivery apparatus and correlation technique.
The content of the invention
Embodiments of the present invention are provided to be used for each location delivery medicine in human patientses or mammal body Device, system, preparation and method.The present invention is directed to delivering of the liquid medicine to patient.The implementation method bag that many is susceptible to Containing delivering liquid medicine by implanted medicament device and its application method.The invention provides a kind of implanted drug delivery Device, it is used for site of delivery such as the blood vessels of liquid drug delivery to patient, but is contemplated that to other site of delivery. In the exemplary embodiment, the embedded type device includes the implantation sandwich type element with outer wall and inner space.Described interior There is mixing chamber in portion space, the wherein mixing chamber (also known as reservoir) is configured to receive the percutaneous conveying to liquid.Multiple is solid Body drug dose also is located in the inner space.The mixing chamber is configured to receive single drug dose, wherein the list Individual solid pharmaceutical dosage dissolving is suspended in the liquid to form the liquid medicine.It is described for delivering liquid medicine Embedded type device further includes conduit, and the conduit is configured to receive the liquid medicine from the mixing chamber and by institute State liquid drug delivery to blood vessel or other site of delivery.
In a preferred embodiment, the mixing chamber has the entry port through the outer wall of the housing, to allow to make Injected with syringe needle and syringe.On the other hand, the preferred embodiment of the embedded type device is further comprising use In the conveying mechanism for advancing single solid pharmaceutical dosage to enter the mixing chamber.It yet still another aspect, the conveying mechanism can be advanced The single solid pharmaceutical dosage passes through the resealable barrier film of the mixing chamber side, split type film etc..In some realities Apply in mode, the single solid pharmaceutical dosage is carried in carousel, the carousel is progressive with by single dose Amount moves to part adjacent with the split type film.
In another preferred embodiment, the embedded type device can further include and be led with described positioned at the mixing chamber Medial compartment between pipe.Preferred embodiment can further include for delivering liquid to the site of delivery through the conduit The pump of drug dose.In the another aspect of preferred embodiment, the embedded type device can further include controller and controllable Valve, wherein the controller mixing that operates the valve to control the liquid in the mixing chamber and the liquid pass through institute State the delivering of conduit.Illustrative embodiments can further include the biography of detection status of patient (for example, hyperglycaemia, arrhythmia cordis) Sensor, wherein the controller is based at least partially on the status of patient that senses to control the delivering of the liquid medicine.
The embedded type device can also include and be configurable to receive the implanted capsule to the percutaneous conveying of liquid.At some In implementation method, implanted capsule is connected to the mixing chamber by implanted pipeline.The capsule can plant with the housing Enter in patient's body, or it can be located at patient in vitro and has towards the housing of the embedded type device and the fluid of mixing chamber and connects Connect, to promote fluid to the conveying in mixing chamber.The mixing chamber in the implantation sandwich type element is configured to receive and From the liquid and single solid pharmaceutical dosage of the capsule, wherein the single solid pharmaceutical dosage dissolves and/or is suspended in described Forming the liquid medicine in liquid.In terms of other of illustrative embodiments, the capsule has entering through its outer wall Inbound port, to allow to be injected using syringe needle and syringe or other fluid delivery devices.
Present invention also offers the application method of the implanted agent delivery device, the method is included in patient's body plants Enter housing and conduit with mixing chamber, wherein the housing carries multiple solid pharmaceutical dosages in the interior volume.One kind is shown The method of example property is further included to the mixing chamber dermal delivery liquid and causes at least one solid pharmaceutical dosage to enter institute Mixing chamber is stated, wherein the solid pharmaceutical dosage dissolves or is suspended in the liquid to form the liquid medicine.The side Method is still further comprised the liquid drug delivery to the blood via the conduit being implanted between the mixing chamber and blood vessel Pipe.
In the preferred embodiment of the method for patient delivery's liquid medicine, dermal delivery includes using pin Head and syringe inject the liquid.However, it is also contemplated that other dermal delivery means as known in the art.Another excellent Select in implementation method, liquid is injected directly into the mixing chamber.Or, liquid is injected directly into implanted capsule and It is set to flow to the mixing chamber from the implanted capsule.In the mixing chamber, the solid drugs dissolve or are suspended in institute State in liquid to form liquid medicine.The liquid medicine is pumped or conduit is directed to, is delivered with feeding to site of delivery. In other implementation methods being susceptible to, the liquid medicine is directed to medial compartment first and is stored until it is required. Then the liquid medicine can be guided or be pumped into site of delivery.
It is described, wherein by fluid dermal delivery to capsule or mixing compartment the method and apparatus being susceptible in, can Mark to help the guiding and placement of transcutaneous fluid delivery apparatus on the skin of the patient.Wherein via syringe needle and syringe Come in the preferred embodiment for delivering fluid, can place on the skin of the patient mark with by the syringe needle be directed to the capsule or The entry port of mixing chamber.
In a preferred embodiment, causing at least one solid pharmaceutical dosage to dissolve or be suspended in liquid includes mixing. In further embodiment, delivering liquid medicine includes that the pumping liquid passes through the conduit.
The medicine can include one or more medicament or other therapeutic agents for treating various diseases and situation.Perhaps Many implementation methods are provided to be used for the embedded type device of the medicine delivery of liquid form to target site of delivery, wherein the medicine (for example, micropill, tablet etc.) storage in solid form, and passed with using syringe or other fluids in compartment/reservoir is mixed Device is sent to be mixed added to the liquid of the mixing compartment via skin entry port (for example, resealable barrier film).It is described The other assemblies of reservoir and described device are installed in implantation sandwich type element, and the implantation sandwich type element is arranged to implantation in vivo Any number of position.The housing includes that at least one is used for the skin entry port to reservoir addition fluid and attachment There is the another port of the delivery members such as conduit.The skin entry port will generally be included to be turned into the wall of the housing The resealable barrier film of one.Preferably, being sized and shaped to housing for being implanted near skin surface, to allow Easily pass through syringe or other skin penetration devices close to the skin entry port.The reservoir also includes resealable Entry port, the resealable entry port can be and the skin entry port identical port.In one or more realities Apply in mode, the reservoir can include the expansible room expanded and pressurize with the addition of fluid, such as bellows.The storage Device has control valve to separate both coupled to medial compartment (being also known as the second reservoir herein).Pressure from the reservoir For driving fluid to enter the medial compartment from the reservoir.The medial compartment is transferred coupled to pumping installations such as Micropumps, The pumping installations is connected to delivery catheter (or other delivery members), and the delivery catheter has and is positioned at the site of delivery Distal end.
Form also is located in the housing for the solid form drug-reservoir of medicine element (medication element). The medicine element may correspond to micropill, tablet or other solid form medicines as known in the art.Each medicine element can One or more medicament containing treatment effective dose.In some embodiments, the medicine element is housed inside packaging and holds In device, the packing container may correspond to airtight or has low permeability to air and vapor in a preferred embodiment Foil paper wrapping container.In a preferred embodiment, solid form drug-reservoir corresponds to the medicine element or their packaging Band attached by container.Generally, the band will be positioned adjacent to or adjacent to the outside of reservoir compartment, and be preferable to carry out In mode, at least a portion of the band around the periphery of the reservoir.Propulsive mechanism is operably coupled to the band, and Medicine element of the propulsion from the band is configured to through the resealable barrier film and is entered among the reservoir.It is described to push away Enter mechanism and generally include drive device, such as micromotor, and the propulsion member promoted by the drive device.It is described Propulsion member may correspond to metal or polymer shaft, and it is configured to promote the medicine element so that it departs from from the band And/or be pushed out its packing container and pass through the resealable barrier film and enter among the reservoir.Once place In the reservoir, the medicine element is just being present in or added to (for example, being added to via the skin entry port) Dissolved in the fluid of the reservoir, to produce the drug solution.
Can be allowed using microprocessor or other controllers by the medicine element added to the solution it Fixed time period afterwards, so as to allow being sufficiently mixed for the drug solution to produce desired medicament dense with the solution Degree.It is sufficiently mixed once having occurred and that, then controls valve to be opened to allow the drug solution to be sent to the medial compartment.One In a little implementation methods, the medicine element is configurable to extremely rapidly be dissolved (for example, in seconds), so as to need not make With control valve.According to other embodiment, described device need not include medial compartment, so that micropump is directly from reservoir aspiration flow Body.In such implementation method, it is possible to use control valve to control the flow of fluid from the reservoir to the micropump.Further Secondaryly, before it there is being sufficiently mixed/dissolve of the medicine element by using approach described herein, it is not necessary to send out The opening of the life valve.
In some embodiments, the reservoir may include hybrid element, magnetic stirring bar or impeller etc., mixing unit Part mixes the fluid in the reservoir to promote medicine element dissolving in the solution.Additionally, in some embodiments, The reservoir may include sensor, be used to determine the drug concentration in the drug solution, and thereby determine the medicine element Whether have occurred and that fully dissolving in the drug solution to produce desired drug concentration.In one or more implementation methods In, the sensor may correspond to the optical pickocff of the optical density for measuring the solution, to be based in this area The technology (for example, using Beer law (Beer ' s law)) known determines drug concentration using optical density.As institute is more detailed herein Carefully describe, the reservoir may also include other sensors, pressure and/or amount for determining the fluid in the reservoir.
In some embodiments, the fluid or drug solution are delivered to from the mixing compartment by pump action The medial compartment.Or, in the embodiments of the present invention, by remaining superpressure by fluid or drug solution from the mixing Compartment is delivered to the medial compartment.The mixing compartment can be configured to spy with elastic (for example, elastic bellows or sacculus) Levy, the elastic construction will flexibly expansion and contraction.In this way, can make to injecting fluid in the mixing chamber described Mixing chamber overpressurization.The fluid with introduce solid drugs therein it is appropriate mix after, controlling the actuating of valve will permit The drug solution is delivered to the medial compartment by the residual pressure for being permitted to come own elasticity mixing chamber, and without the operation of pump.
In some embodiments, the fluid is delivered to by the mixing compartment from reservoir by pump action.Entering In implementation method of one step comprising reservoir, the reservoir can be also characterized with the construction of elastic type, and the construction will be allowed The elastic dilatation of the reservoir and contraction.In this way, the reservoir can be made excessively to increase to injecting fluid in the reservoir Pressure.Controlling the actuating of valve will allow the residual pressure from the reservoir that the fluid is delivered into the mixing chamber, and nothing Need the operation of pump.
The micropump is configured to draw liquid from the medial compartment, and is pumped to target delivering by the conduit Position, such as vein, artery, organ or muscle.The micropump can be by microprocessor or other controllers described herein To control, to control one or more in delivering amount and delivery rate of the drug solution to the site of delivery.In addition, one Control can separate the medial compartment with the micropump.In each implementation method, the micropump is configurable to deliver body Product drug solution of the scope from 1 μ l to 100ml.It can also configure the presence for detecting bubble in solution, to stop and/or Disintegrate the bubble.It can also be programmed for regularly pumping solution through the conduit, with keep the conduit or other Delivery member it is unobstructed.
One or more operations of the agent delivery device can be controlled by controllers such as microprocessors.It is such Operation can for example include：Mixing in the mixing compartment；The operation of the micropump；And by the mixing chamber with it is described Medial compartment/storage chamber be connected and the medial compartment is connected with the micropump one or more control valves operation.The dress Putting may include one or more sensors and performs following one or more：I) when detection is in mixing chamber addition Fluid；Ii) detection the first reservoir in the solution in when obtain being sufficiently mixed so as in the solution produce expectation Drug concentration；Iii) detect the mixing chamber and/or medial compartment in when exhausting fluid；And iv) detect any reservoir Whether pressure is down to below specific threshold.In both of the latter cases, the sensor can then send to the controller and believe Number, to remind user to need to add more fluid to the reservoir.The prompting can be the audible alarm means in described device, And/or the portable phone that is sent to of alarm signal that is sent in described device or other portable communication devices etc. Sound or other alarms (for example, visual alarm, haptic alerts) on external equipment.
It is in some applications, described that site of delivery (position that the medicine delivery is arrived) can (medicine be pre- with target site Phase reaches and/or the position with curative effect or other effects) it is identical.In other application, the target site may differ from described Site of delivery, for example, the site of delivery can be the intramuscular tissue in chest, and the target site can be heart or liver It is dirty.The site of delivery can be adjacent to the target site, such as adipose tissue, to be delivered to bottom musculature；Or its Non- opposing parts are placed in, for example, intramuscular delivers to arrive at heart.
In the respective applications, embodiments of the present invention can be used to deliver drug solution to provide to being sent out including such as epilepsy Work, hypertension, high cholesterol, diabetes, coronary heart disease and arrhythmia (including room and room property), coronary ischemia (for example, by In heart attack), cerebral ischemia, apoplexy, anaemia or other similar states interior various medical conditions treatment.Described device It is implanted at the target site or near it, or is implanted in remote delivery position (for example, the intramuscular in chest or thigh Implantation), and the conduit or other delivery members are positioned at the target site nearby or coupled to vein with by vein It is interior delivering and arrive at the target site.
In for the illustrative embodiments using the method for the present invention, the implementation method of described device is implanted in choosing Fixed site of delivery, such as arm, leg or buttocks.Desirably, described device subcutaneously implantable but sufficiently close to skin table Face, so as to approach the barrier film on first reservoir by the needle-like syringe inserted through skin, with to described Reservoir adds salt solution or other fluids.Implantation can be used open or micro-wound surgical operation program as known in the art to enter OK.Before implantation, described device can be loaded micropill (or other solid dosage forms with selected number described herein Medicament, for example, tablet etc.) one or more band or other drugs, to provide long-term (example of the micropill to the site of delivery Such as, the several years) delivering.Once implantation, the micropill (for example, 1 year, 2 years, 5 years or for more time) can be stored in the dress for a long time In putting and without degraded or to the illeffects (for example, loss of dose efficacy or curative effect) of the micropill.When micropill be stored in it is close Situation is particularly true when among the packing container of envelope.Described device can be programmed (for example, by controller, such as microprocessor Or other logical resources as known in the art) for (for example daily, weekly, monthly etc.) at regular intervals or in response to The input from sensor as described herein and deliver medicine to the site of delivery.In the case of the latter, the input Can indicate that the event such as specific medical situation (for example, hyperglycaemia) or epileptic attack or breaking-out earlier event.It is described herein Controller can be used for based on sensor be input into and/or using regular intervals of time delivering embodiments of the present invention Delivery time It is spaced to determine when to start delivering.In any case, the controller can be to the micropump or other pumping installations Sending signal, to deliver the liquid medicine of doses to the site of delivery.
Embodiments of the present invention can be used to provide the synchronous therapeutic to two or more medical conditions, so as to eliminate trouble The need for person took the various medicaments (for example, orally or through parental routes) of multiple dosage in the middle of one day.For suffering from The patient of long-term chronic situation (for example, diabetes, Parkinson's disease, epilepsy, AIDS, cancer etc.), including those for example due to Dull-witted or Alzheimer's and for causing the impaired patient of cognitive ability, this is particularly advantageous.In use, such reality The mode of applying is favorably improved compliance of the patient to one or more the medicament schemes for the situation for the treatment of, thus improves clinical knot Really.
The further detail below of these and other embodiment and aspect of the invention is described more fully with below with reference to accompanying drawing.
Quote and be incorporated to
All publication, patents and patent applications mentioned in this specification are incorporated by reference into this, and degree is still As specifically and individually pointed out to be incorporated by reference into each indivedual disclosures, patent or patent application.
Brief description of the drawings
Novel feature of the invention is specifically explained in the appended claims.By reference to following to wherein using this The detailed description and the accompanying drawings that the Illustrative implementation method of inventive principle is illustrated by, it will to the features and advantages of the present invention It is better understood from；In the accompanying drawings：
Fig. 1 illustrates the implementation method of agent delivery device, it include the first reservoir and the second reservoir, micropump and Solid chemicals are supplied.
Fig. 1 a and Fig. 1 b are illustrated for the implementation method to the resealable barrier film of delivery of solids medicament in the first reservoir.
Fig. 1 c are the block diagrams of the various sensors that diagram can be used together with the implementation method of agent delivery device.
Fig. 2 illustrates the reality of solid chemicals band and the propulsion plant for being advanced to solid chemicals micropill in the first reservoir Apply mode.
Fig. 2 a illustrate the implementation method for the propulsive mechanism being advanced to solid chemicals micropill in the first reservoir.
Fig. 3 illustrates the curve map of drug concentration and optical density, and it can be used to distinguish the medicine in the mixing chamber reservoir Agent mixability.
Fig. 4 illustrates the implementation method of agent delivery device, and the agent delivery device includes：Reservoir, the reservoir is coupled to Fluid cell for filling the reservoir；Micropump；Conduit；And solid chemicals supply.
Specific embodiment
Embodiments of the present invention provide be used for the device of each location delivery medicine in body, system, preparation and Method.Many implementation methods provide the implanted device of the medicine for delivering liquid form, wherein the medicine is included for controlling Treat one or more solid form medicament of various medical conditions such as epilepsy, diabetes, hypertension and high cholesterol or its His therapeutic agent.Particular implementation provides the implanted device of closing, for site of delivery DS and finally to such as brain or the heart The target tissue site TS (herein referred as target site TS) such as dirty delivers medicine/drug solution, with long-term treatment medical conditions.
Referring now to Fig. 1-Fig. 4, the implementation method for the device 10 to site of delivery DS delivering drug solutions 101 includes shell Body 20, the housing 20 contains the first reservoir 30 (also known as mixing chamber 30), the second reservoir 40 (also known as medial compartment 40), pump installation 50th, delivery member 60, controller 70, power source 80, medicine propulsive mechanism 90 and one or more solid form medicines are contained The drug-reservoir 105 of element 100.One or more in reservoir 30 and reservoir 40 and pump installation 50 can be by connecting pipe 11 may correspond to other attachment means 11 of polymer pipeline as known in the art and be attached.In addition, reservoir 30 and storage One or more in device 40, pump installation 50 and delivery member 60 can have the controlled valve 54 being located between them, to control Make the flow of fluid from upstream chamber/device to the downstream.In certain embodiments, control valve 55 can be placed on reservoir 30 Between reservoir 40, and another 56 can be placed between reservoir 40 and pump installation 50, and be contemplated that to other positions.Control Valve processed 54 may correspond to various miniature electronic control valves as known in the art, such as various miniature electromagnetic valves and leaf valve.
As discussed in this article, solid form medicament element 100 is arranged to water or the aqueous solution (example in reservoir 30 Such as, salt solution) middle dissolving, to form drug solution 101.Element 100 generally will be comprising for treating one or more situation (example Such as, epilepsy, arrhythmia cordis, diabetes etc.) medicament 102, and one or more auxiliary material 103, such as disintegrant, preservative, Binding agent etc..In a preferred embodiment, auxiliary material 103 includes disintegrant as known in the art to promote the element in water And/or the dissolving in other aqueous solution used in salt solution or pharmaceutical field.Element 100 can have correspond to micropill, tablet, One or more in caplet, cylinder and pharmaceutical field in known other solid forms of shape.For ease of discussing, now by it Be referred to as medicament pellet 100 or micropill 100, but every other form described herein is equally applicable.According to one or many Individual implementation method, micropill 100 can be stored in pierceable packing container airtight as discussed in the text.
Housing 20 is configured to be implanted under skin S, and including for the syringe needle 111 by needle-like syringe 110 or Other tissue-penetrating elements 111 are come one or more salable ports 23 for penetrating.Salable port 23 generally will include by The salable barrier film 23 of various elastomeric material (for example, polysiloxanes, polyurethane) manufactures.In some embodiments, it is salable Barrier film 23 can be same barrier film with the salable barrier film 33 on reservoir 30, or not so be adjacent.Mark In is indicated in patient Skin on.Mark In is used for helping the guiding and placement to syringe needle 111.Housing 20 may also include for conduit or other deliverings The opening 24 of the attachment of component 60.Its size and in addition its shape can be set to be placed in patient's body or On multiple positions, for example, including the position in one or more in patient, arm, leg, trunk or chest area. Additionally, its size and in addition its structure can be set to be positioned in flesh upper bit and intramuscular site, the example of the latter Biceps, triceps or muscle of thigh including patient.Generally, it will have the cylindrical shape with circular distal, but also set Expect other shapes.It can be made up of biocompatibility metal and/or polymer, and with tissue contacting surface 21 and inside Space 22.Tissue contacting surface 21 can include various biocompatible polymers as known in the art and/or polymer coating, For example, including polysiloxanes, polyurethane and polytetrafluoroethylene (PTFE) (PTFE).
In each implementation method, whole housing 20 or one part can by adaptive material (for example, polyurethane-polysiloxane and Other elastomeric polymers) it is built-up, to accord with the shape of surrounding tissue layer and/or the shape of its tissue compartments being put into, example Such as, the profile of bladder, vagina, gall-bladder etc., or cover the profile of the skin of implantation position.Can also be allowed using adaptive material Surrounding body tissue grows and reinvents housing in the long period is implanted into around housing.In this way, with flexible shell Implementation method housing is minimized the growth of surrounding tissue and the influence of function, so as to allow by device implantation it is very long when Between, including allow that device is implanted into children's body and adult is remained to.Various adaptive materials are it is also possible to use to help using minimally invasive Method implanted device 10.Such material allows to include device bending, the distortion or otherwise conformal of housing 20, so as to through outer Section's surgical port and guide are inserted and then recover its shape if predetermined implant site is positioned at.In particular implementation side In formula, the bending and distortion of housing 20 can be further promoted by using the flexible joint being built among housing.Can also set The size and dimension of fixed shell 20 further promotes to be implanted into using micro-wound surgical operation method.For example, housing can have The shape of specific dimensions and such as cylinder etc, allows it to through various micro-wound surgical operation ports and guide. Housing may be additionally configured to the deployable state of non-deployment state and expansion with collapse, and wherein non-deployment state is used to advance shell Body, and if the desired locations that housing is positioned in body it is deployable state.
In one or more implementation methods, the first reservoir 30 may correspond to distensible devices, such as distensible ripple Pipe, it can expand and pressurize with the addition from the fluid 109 of syringe or other fluid delivery devices 110.It is contemplated that To other distensible devices such as expandable balloons, the reservoir 30 includes resealable barrier film 33, for by syringe 110 Into to inject the salt solution or other fluids from the syringe or other fluid delivery devices 110 (for example, pump etc.) 109.Barrier film 33 can include various sealable elastomers, such as polysiloxanes or polyurethane.In some embodiments, barrier film 33 is same barrier film with the barrier film 23 on housing 20, or is not so adjacent.For example, in certain embodiments, barrier film 33 The underface of barrier film 23 is can be placed in, and can be attached thereto.Reservoir 30 may also include another resealable barrier film or port 35 (further detailed herein), the resealable barrier film or port 35 are configured to allow by propulsive mechanism 90 by micropill Or other solid drugs elements 100 are inserted into reservoir.Added to reservoir by syringe 110 or other fluid delivery devices Before or after fluid, micropill 100 can be inserted into reservoir.In any case, micropill is arranged to dissolving with shape Into drug solution 101.Once inserting solution, reservoir 30 just has internal pressure, and the internal pressure is subsequently used in the second reservoir 40 supply fluids, second reservoir 40 can also correspond to expansible bellows but with the size smaller than reservoir 30.Using next Filling from the fluid of reservoir 30 to reservoir 40 can be controlled by control valve 55, according to one or more implementation methods, the control Valve 55 can be controlled by controller 70 or other control systems (for example, peripheral control unit).Reservoir 40 transfers to be filled coupled to pumping 50 (such as micropumps 50) are put, the pumping installations 50 is connected to the delivery catheter 60 positioned at the distal end 61 of site of delivery DS.
The bank 105 of solid form medicament 100 is coupled to the side of reservoir 30, and can be worn via the insertion of delivery mechanism 90 Cross resealable wall or the port of reservoir 30.Micropump 50 is configured to draw liquid from reservoir 40 and passed through the pump of conduit 60 Deliver to target site of delivery DS, such as vein, organ or muscle.Micropump 50 can also configure for deliver microlitre or milliliter in the range of Optional dosage liquid medicine 101.It is contemplated that arriving other scopes.
In each implementation method, one or more operations of agent delivery device 10 can be controlled by controller 70.Control Device 70 may correspond to microprocessor or other logical resources (for example, state device, analogue means etc.) as known in the art, and And may also include memory resource, RAM, DRAM, ROM etc..The logical resource and/or memory resource may include for One or more software modules of the operation of controller.By using module, controller 70 can be programmed for including medicine delivery Scheme, its is medium-term and long-term with fixed intervals (for example, once or twice daily etc.) delivering medicine/drug solution.Controller 70 may be used also Including the RF devices for receiving wireless signal (for example, wirelessly or otherwise), passed to start medicine delivery or change Send scheme (for example, being faded to twice daily from once a day).In this way, patient or provider may be in response to Particular event (for example, angina pectoris attacks) or status of patient or the longer-term of diagnosis change to control the delivering of medicine.
The operation of the device 10 that can be controlled by controller 70 can for example include：Mixing in reservoir 30 is mixed；It is miniature The operation of pump 50；The operation of one or more controls valve 54 (for example, valve 55, valve 56 and valve 57)；And micropill propulsive mechanism 90 Actuating and control.This generic operation can be helped by using one or more sensors 84.According to each implementation method, sensing Device 84 is configurable to perform one or more following functions：I) when detection is in mixing chamber addition fluid；Ii) detect When 101 in obtaining being sufficiently mixed so as to producing desired drug concentration in the solution；Iii mixing chamber and/or medial compartment) are detected In fluid amount in when being down to below given threshold；And iv) detect whether the pressure in any reservoir is down to given threshold Below.In all four cases, particularly in the case of both rear, described device (for example, by using controller 70) Can be configured to via the sense of hearing/haptic alerts from the device and/or via the alarm signal transmitted from described device Feelings as user are reminded in the sense of hearing of number portable phone or other portable sets that are sent to, tactile or other alarms Condition.Additionally, in each implementation method, controller 70 can be programmed for include delivering scheme, its it is medium-term and long-term with select it is regular between Every (for example, once or twice daily etc.) delivering medicine.It can also configure for receiving signal (for example, wirelessly or with its other party Formula) to start medicine delivery or to change delivering scheme (for example, being faded to twice daily from once a day).In this way, Patient or provider may be in response to particular event (for example, angina pectoris attacks, epileptic attack etc.) or status of patient Or longer-term change (for example, insulin tolerance increase) of diagnosis carrys out the delivering of titration of medicines.
According to one or more implementation methods, controller 70 can be operably coupled to one or many in sensor 84 Individual and input of the reception from it, the sensor is for example included in sensor 85, sensing shown in the implementation method of Fig. 1 c One or more sensors in device 86, sensor 87, sensor 88 and sensor 89.In one embodiment, controller Coupled to the sensor 85 in reservoir 30 to receive input 85i, input 85i indicate pressure in reservoir and/or The Fluid Volume of presence.As described herein, the liquid level or pressure that such input 85i can be used in reservoir 30 are down in reservoir User/patient is reminded when below given threshold.Sensor 85 may correspond to pressure sensor as known in the art (for example, solid State strain gauge) or fluid volume sensor in one or more.
In another embodiment, controller is operably coupled to sense and indicates and to be come by the medicament in medicament pellet The sensor 86 of the physiological parameter of the situation for the treatment of, for example, be used to sense diabetic hyperglycemia (its can by insulin or Its analog or derivative are treated) glucose sensor.Indicate what is had troubles when controller 70 is received from sensor 86 During input 86i, it starts the actuating of micropump or other pumping installations 40 to deliver the dosage of drug solution 101.From sensing The delivering that the initial input of device 86 and follow-up input are used equally to long-term titration of medicines solution is dissipated or with it until the situation He obtains medical treatment at mode.Sensor 86 is typically implanted, but and differs such as in the case of glucose sensor like that It is fixed such.In some cases, sensor 86 can be worn or carried by by patient, such as measuring pulse frequency and/or Po2Level And be inputted 86i via RF signals or other transmission means and transmit to the sensor of controller 70.
Controller 70 can also receive its from the blood or other tissue concentrations for being arranged to the medicament that measurement is delivered The input 87i of his sensor 87.These inputs can also be used for the delivering of titration of medicines solution 101 to realize selected drug concentration (for example, the drug concentration among blood plasma, tissue etc.) and selected Pharmacokinetic Characteristics are (for example, Cmax、tmax、t1/2 Deng).Medicament sensor 87 can be positioned on target tissue site TS and in vivo other positions (for example, vein or artery), to build The pharmacokinetic model of the medicament distribution in three-dimensional on multiple position.
Described device may also include the sensor coupled to controller 70, and the sensor is indicated and remained in the first reservoir 30 Remaining how much solution 101 and/or the remaining how many medicament pellets 100 in bank 105.Controller transfers that the information can be signaled To external communication device, such as cell phone, portable monitor or remote monitor (for example, positioned at office of doctor). In in this way, patient and/or provider can exhaust medicament pellet 100 and/or medicine far away from described device Appropriate action is just taken before solution 101.
According to one or more implementation methods, drug-reservoir 105 corresponds to one or more bands 106, and the band 106 has many The medicament pellet 100 of individual attachment or the packing container 104 containing the micropill of attachment.Band 106 can comprising polymer film or Metal foil or other thin-film materials.Container 101 can be along the surface attachment of packing container main body to band 106, or they can collect Band 106 is attached to middlely or is otherwise integrally formed therewith.Such implementation method can by by same material bar or other Sheet material (for example, polymer film, metal foil etc.) manufactures band 106 and container 104 to realize.Container 104 can be used in this area The various attachment methods known and be attached to band 106, the attachment method include adhesive bonding, ultrasonic bonding, RF weld and Other method.In each implementation method, packing container 104 can be comprising known various salable paper tinsels in drug packing field and poly- Compound, for example, PET, HDPE and other materials as known in the art.In some embodiments, container 104 can have bilayer Construction, to improve impermeability.
In many embodiments, with 106 around the outer surface of reservoir 30.The side of being preferable to carry out of shown band in fig. 2 In formula, with 106 around with cylinder or columnar capsule shape (for example, being similar to hot dog shape) reservoir 30 reality Apply the periphery 30c of mode.As discussed herein, including delivery mechanism 90 be used for bonding ribbon 106 and by single medicament pellet 100 from The band is transported to reservoir through other the salable ports 35 in the salable barrier film 36 and/or the reservoir of reservoir wall 30w Internal 31.In this place, the medicament pellet is dissolved in fluid 109 existing in reservoir 30 or being added to.In many realities Apply in mode, the delivery mechanism includes the propulsion member 91 and propulsion plant 92 as shown in the implementation method of Fig. 2 and Fig. 2 a. For the implementation method with the micropill 100 (or other solid form medicines 100) being stored in packing container 104, pushing-in member Part 91 be can also configure for piercing through packing container, and micropill is released and through the salable of reservoir port or reservoir from the container Partly it is pushed among reservoir.Delivery mechanism 90 it is also expected to be configured to push belt 106 so as to by another packing container with Propulsion member is aligned, so that next micropill is to the delivering in reservoir.This can be realized by being indexed to the band.Propulsion dress Putting 92 will generally be powered by power source 80 (for example, electrochemical cell), but in some embodiments, can have its own Single power source.
In many embodiments, delivery member 60 corresponds to flexible conduit 60, and the flexible conduit 60 is coupled to opening 24 Or other openings in housing 20.Conduit 60 have be chosen to be for drug solution 101 to be delivered into selected site of delivery DS Length.The internal diameter of conduit 60 can be chosen to be the permission drug solution and flow through conduit in the case of without notable fluid resistance. Conduit 60 can be made up of one or more biocompatible polymer as known in the art, and the biocompatible polymer is all If any PeBax, polysiloxanes, polyethylene, polyurethane etc..Desirably, the distal tip 62 of the conduit is matched somebody with somebody with hurtless measure Put, to allow to be chronically implanted in target site of delivery DS and the foreign body reaction such as nothing inflammation.Including tip 62 conduit 60 and The other parts of device 10 may also include antimicrobial coating, such as various antibiotic and silver coating, so that bacterial adhesion and/or infection Minimize.Such coating can be additionally used in the other parts of device 10, including housing 20, reservoir 30 and reservoir 40 and pump 50 In one or more.In some embodiments, device 10 may include multiple conduits 60 to allow to use single delivering dress Put 10 and drug solution is delivered to multiple site of delivery.For example, in one embodiment, device 10 may include to be positioned at vein In the first conduit 60 and be positioned at the second conduit 60 of intramuscular site.In use, such implementation method provides particular agent Different delivery rates and relevant pharmacokinetic.For example, systemic delivery can be provided to realize the blood concentration of medicament Quickly raise (for example, shorter tmax, but less t1/2), and can be delivered using intramuscular and to realize slower delivery rate (t more longmax) but medicine delivery with longer-term (for example, larger t1/2)。
Desirably, micropill 100 is configured in liquid 109 rapid dissolving has desired medicament in the solution to produce The drug solution 101 of concentration.In order to allow time enough to be dissolved for as, controller 70 can be configured to true It is set to and is sufficiently used for remaining turned-off the control valve 55 between reservoir 30 and reservoir 40 in the setting period of solution micropill 100. In some implementation methods, micropill can be promoted by using the mixing arrangement of such as hybrid element 39 etc as mentioned below 100 dissolving in solution 109.In other embodiments, by heating element heater (not shown) and/or can use patient's Body heat come promote dissolving (in the case of the latter, one or more in housing and/or reservoir 30 can be made from a material that be thermally conductive, with Heat from patient is conducted to reservoir).Additionally, in each implementation method, can for example by using one or many Individual sensor 84 come control solution 101 mixing and/or in fluid 109 dissolve medicine 100 time.In particular implementation In mode, such sensor may correspond to sensor 89, and the sensor 89 is selected for determining the medicine in drug solution 101 Agent concentration, and thereby determine whether medicament pellet 100 has occurred and that fully dissolving is to produce the desired medicine in drug solution 101 Agent concentration.In one or more implementation methods, sensor 89 may correspond to optical pickocff, and it is used to measure solution 101 Optical density, to be based on technology as known in the art (for example, using Beer law), to determine medicament using optical density dense Degree.Sensor 89 can be located on the outer surface of reservoir 30 in (as shown in Figure 2) or internally positioned 31, and can be operable Ground is coupled to controller 70 to send the input 89i of the optical density indicated in solution 101 to controller.As shown in Figure 3, The mathematical correlation 120 between the drug concentration in optical density and solution 101 can be set up using such technology.Additionally, By using such correlation 120, it may be determined that for the floor level 131, optimum level of the drug concentration in solution 101 132 and the threshold value 130 of highest level 132.According to an implementation method, controller 70 (or other control systems) allows to dissolve Journey at least lasts till lowest threshold 131, and more desirably lasts till optimal threshold 132.When such threshold value is reached, control Device then allows for solution 101 to be delivered to reservoir 40 from reservoir 30 via the control of valve 55.Controller can also send to user (for example, via portable set, such as cell phone) indicates the signal for having occurred and that such case.In addition, if due to Certain reason, the drug concentration in reservoir exceedes threshold value 133, then controller can be to user's sending signal (for example, via portable Equipment or other communication equipments) with to the fluid of the addition specified quantitative of reservoir 30, to reduce fluid concentrations.During this period, control Device can stop further to reservoir 40 and/or the delivering solution 101 of micropump 50.For the implementation of the device 10 including fluid cell 45 Mode, controller can also receive more fluids to the sending signal of control valve 57 that capsule 45 is connected to reservoir with from the capsule. In such implementation method, can be by the pressure in capsule or the fluidly hand of the pump that be coupled for capsule 45 and reservoir 30 by (not shown) Section sucks fluid.
According to one or more implementation methods, can be by using one or more hybrid elements being placed in reservoir 30 39 promote the dissolving of micropill 100.According to one or more implementation methods, hybrid element 39 may correspond to various magnetic stirring bars (desirably scribbling inert material), its magnetic field that can be generated by the implementation method of the propulsion plant 92 comprising rotating electromagnetic motor To drive.According to other embodiment, hybrid element 39 may correspond to impeller, its be operably coupled to propulsion plant 92 and/ Or mechanism 90.In any case, controller 70 can be configured to by fluid 109 and micropill 100 added to reservoir situation Under, the mixing of fluid 109 is started by element 39.By using reservoir 30 and reservoir 40 can be positioned at as the case may be In or in addition with one or more sensors 84 of its fluid coupling, it is possible to achieve to reservoir 30 (or reservoir 40) internal memory Fluid 109 detection.The input from sensor 89 is it is also possible to use to control hybrid element 39.
Power source 80 may correspond to various miniature electrochemical cells as known in the art, such as lithium battery, lithium-ion electric Pond or other batteries, and or many in controller 70, pump installation 50, control valve 54 and propulsive mechanism 90 can be coupled to It is individual.It may be configured to can be by being conductively coupled to be located below the sheet on the region of the skin S for being implanted with device 10 Known charging source is recharged in field.
In many embodiments, port 35 includes salable barrier film 36, so that as illustrated in the embodiment of fig. 1 Allow to make the medicine 100 of solid dosage enter into enclosure interior 31 without fluid through the barrier film by mechanism 90.Barrier film 36 Can be comprising various elastomeric polymers as known in the art such as polysiloxanes or polyurethane, it is configured to have enough Elasticity with by medicament pellet 100 through pierce through or otherwise open after open and then seal its own. In particular implementation, as shown in the implementation method of Fig. 1 a and Fig. 1 b, barrier film 36 can have reclosable slit 37, should Slit 37 under normal circumstances be close, and by medicine 100 through and opens, only medicine 100 pass through after just because of structure Itself is closed again into the elasticity and resilience of the material of barrier film 36.
Additional or in alternative embodiment, as shown in the implementation method of Fig. 4, fluid 109 can be by means of capsule 45 And reservoir 30 is added to, the capsule 45 is fluidly coupled to reservoir 30 by means of connecting pipe or other fluid-coupling devices 47.Also Control valve 57 (can be controlled by controller 70 or other control systems) can be positioned between capsule 45 and reservoir 30, to control fluid 109 from capsule to reservoir 70 flowing.Similar to reservoir 30, capsule 45 can be configured by injecting fluid 109 and be pressurized, to make The pressure is obtained to be enough to provide the driving force for the flow of fluid between capsule 45 and reservoir 30.Or, can be by pump or other pumpings Device (not shown) is fluidly coupled to capsule 45 and reservoir 30, and fluid is pumped into reservoir from capsule.The use of such secondary pumps Can be controlled by controller 70 or other control systems.
Generally, as shown in the implementation method of Fig. 4, capsule 45 can be configured to (for example, being subcutaneously implanted) of implanted.However, In other embodiments, capsule 45 is positioned using the connecting pipe or other fluid-coupling devices 47 of the skin through patient It is external in patient.In such implementation method, capsule 45 can be configured to be worn by patient or is otherwise carried.For implanted Implementation method, capsule 45 will generally include the resealable barrier film 46 similar to barrier film 23 or other resealable ports 46, use In by syringe or other fluid delivery devices 110 come subcutaneous delivery of fluids 109.The non-built-in mode implementation method of capsule 45 also may be used Including such barrier film 46.
Fluid 109 from capsule 45 can be used for reservoir pressurize and/or with micropill 100 or other solid form medicaments 100 Form drug solution 101.Such fluid may include for mixed with micropill 100 in reservoir 30 water, salt solution or other The aqueous solution.Capsule 45 can be fabricated by by the biocompatible polymer of various impermeable liquid water/gas bodies as known in the art, institute The example for stating polymer includes polyisobutyl rubber and one or more copolymer.It can have appearance of the scope in 5 to 300ml Product, but be contemplated that to other volumes.Capsule 45 may also include one or more sensors 88, be used to sense the pressure and stream in capsule 45 One or more among the amount of body 109.Sensors with auxiliary electrode may include that various pressure sensors as known in the art, optics are passed Sensor and/or impedance transducer.Similar to the use of the sensor 85 in reservoir 30, sensor 88 can be used for by controller 70 Sent to patient when one or more in volume or pressure in capsule 45 are reduced to below threshold level and reminded.
Desirably, including band 106 sufficient supply of the bank 105 containing medicament pellet 100, so as to long-term (for example, 2 to 5 Year or longer time) treatment of the offer to specific medical situation.In each implementation method, band 106 can accommodate it is up to hundreds of or More micropills 100.In each implementation method, device 10 may include multiple bands 106, including can be around whole bellows reservoir 30 Or part thereof of 2,3 or more bands.In these implementation methods and related embodiment, device 10 may include for Second is switched to 106 device from first band 106.Such switching device (it is not shown, but can easily by electro-mechanical arts Technical staff is understood) can for example include solenoid, and can be independent or be incorporated into micropill propulsive mechanism 90 (also known as It is propulsive mechanism) among.
Discussion now is made to delivery mechanism 90 (being also known as propulsive mechanism 90, the mechanism 90 of this paper sometimes).In many realities Apply in mode, mechanism 90 includes propulsion member 91, the propulsion member 91 is coupled to propulsion plant 92, and the propulsion plant 92 can be corresponded to In micromotor, including line inductance electromotor.Propulsion plant 92 also corresponds to piezo-electric device, and it can be configured in response to example Tathagata deforms and moves from the applied voltage of controller 70 and/or power source 80.In each implementation method, propulsion member 91 pairs Should be in silk thread or plastic shaft, it is configured with enough column intensities to promote micropill 100 through barrier film 36 and enter into storage Among device 30.The implementation method in packing container 104 is comprised in for micropill 100, propulsion member 91 is additionally configured to (example Such as, by column intensity etc.) packing container is pierced through, and micropill 100 is released into the container and barrier film 36 is passed through.This can be wrapped Include taper or the pointed tip propulsion member 91 being configured with for piercing through packing container 104.
In implementation method substitute or additional, band 106 may include single tape drive mechanism (not shown), and the band drives Motivation structure may correspond to sprocket wheel, gear etc. or be configured to other the engageable propulsion plants driven by mechanism 90.Institute Stating single drive mechanism can couple directly to mechanism 90 (for example, via gear or other mechanical linkages), or can be through From the hand of the controller 70 in response to the input or the signal that are sent to mechanism 90 and to the single drive mechanism sending signal Section to be coupled to mechanism 90 indirectly.
In for the illustrative embodiments using the method for the present invention, the implementation method of device 10 is implanted in selecting Site of delivery DS at or its near, such as arm, leg, buttocks or blood vessel.For site of delivery DS be blood vessel (for example, quiet Arteries and veins or artery) implementation method, described device is implanted in the tissue of selected near vessels, and then by the remote of conduit 60 The distal part at end 62 or bigger is positioned in the blood vessel.Desirably, described device is implanted subcutaneously, but sufficiently closes to skin Surface S so that (or other fluids of syringe needle 111 for the syringe 110 that the barrier film 23 on the first reservoir 30 can be by inserting through skin Delivery apparatus) entered, to add salt solution or other fluids to reservoir.Putting for syringe needle 111 can be helped using mark In Put and guide.Implantation can be used open or micro-wound surgical operation program as known in the art to carry out.Before implantation, can be by Device 10 load with selected number micropill (or medicine of other solid dosage forms) one or more band 106 (or its His drug-reservoir 105), delivered to long-term (for example, the several years) of site of delivery with providing micropill.Once implantation, micropill can be long-term (for example, 1 year, 2 years, 5 years or longer time) storage in said device and without degraded or to the illeffects of micropill (for example, The loss of dose efficacy or curative effect).Described device can be programmed (for example, by controller 70) at regular intervals (for example, Daily, weekly, monthly etc.) or in response to the input from one or more sensors 86 (such as glucose sensor) 86i to deliver medicine/drug solution to site of delivery.In the case of the latter, the input can indicate that specific medical situation (for example, hyperglycaemia) or event, such as epileptic attack or breaking-out earlier event.Controller 70 is configurable to based on sensor The Delivery time of the embodiments of the present invention of the input of 86 (or other sensors) and/or the medicine delivery of use regular intervals of time It is spaced to determine when to start delivering.In any case, controller can send letter to micropump 50 or other pumping installations Number it is delivered to one or more site of delivery DS with by the liquid medicine 101 of one or more dosage.
Conclusion
Being described above for each implementation method of the invention is described for the purpose of illustration and description.The present invention is not It is intended to be limited only to exact form disclosed.Many modifications, changes and improvements will for this area working technical staff It is obvious.For example, can by the implementation method of device be sized and otherwise adapt to various children using and Neonate applies.Additionally, the embodiments of the present invention can be sized and otherwise adapt to various veterinary applications, For example include one or more among ox, horse, pig, dog, cat.In such cases, it is possible to use embodiments of the present invention To deliver various antibiotic, antiviral agent and other medicaments of the various common diseases for treating or preventing performing animal.
From an element for implementation method, characteristic or action can easily with one from other embodiment Or multiple elements, characteristic or action are reconfigured or replaced by it, to form the numerous additional reality belonged in the scope of the invention Apply mode.Additionally, be depicted and described as can be in each implementation method as independent element with the element that other elements are combined And exist.Therefore, the scope of the present invention is not intended to be limited to the detail of described implementation method, but it is opposite only by Appended claims are limited.
Although the preferred embodiment of the present invention has been illustrated and described herein, for those skilled in the art Speech will be evident that such implementation method is provided simply by the mode of example.Without departing from feelings of the invention Under condition, those skilled in the art will make many changes, change and substitute.It should be appreciated that of the invention putting into practice During can using embodiments of the invention described herein various alternative solutions.Following claims is intended to limit The scope of the present invention, and therefore cover the method and structure and its equivalents belonged in these rights.

Claims (12)

1. a kind of embedded type device of vascular delivery liquid medicine for patient, described device is included：
Implantation sandwich type element, it has outer wall and inner space；
For receive liquid percutaneous conveying and in the inner space by the liquid and multiple solid pharmaceutical agents The device that amount is mixed, wherein single solid pharmaceutical dosage is dissolved in the liquid to form the liquid medicine；And
Conduit, its be configured to receive the liquid medicine from mixing chamber, and for by the liquid drug delivery extremely The blood vessel,
Wherein described percutaneous conveying for receiving liquid and for consolidating the liquid and multiple in the inner space The device that body drug dose is mixed is included：
Implanted reservoir, its percutaneous conveying for being configured to receive liquid；And
Mixing chamber, it is configured to receive liquid and the single solid pharmaceutical dosage from the reservoir, wherein the list Individual solid pharmaceutical dosage is dissolved in the liquid to form the liquid medicine.
2. embedded type device according to claim 1, wherein the reservoir and the mixing chamber are installed in housing.
3. embedded type device according to claim 1, wherein the reservoir is installed in the outside of the housing, and it is described Mixing chamber is installed in housing.
4. embedded type device according to claim 3, wherein the implanted reservoir is connected to by implanted pipeline The mixing chamber.
5. embedded type device according to claim 1, wherein the reservoir has the entry port through its outer wall, so as to Allow to be injected using syringe needle and syringe.
6. embedded type device according to claim 1, further includes conveying mechanism, and the conveying mechanism is used for will be single solid Body drug dose is advanced into the mixing chamber.
7. embedded type device according to claim 6, wherein the mechanism advances the single solid pharmaceutical dosage to pass through Split type film in the side of the mixing chamber.
8. embedded type device according to claim 7, wherein the single solid pharmaceutical dosage is carried on disk transmission In band, the carousel is progressive to move to part adjacent with the split type film with by the single solid pharmaceutical dosage.
9. embedded type device according to claim 1, further includes pump, and the pump is used for through the catheter delivery liquid Drug dose.
10. embedded type device according to claim 1, further includes controller and controlled valve, wherein the controller The valve is operated, to control mixing and the liquid of the liquid in the mixing chamber to pass through the delivering of the conduit.
11. embedded type devices according to claim 10, further include to detect the sensor of status of patient, wherein described Controller is based at least partially on sensed status of patient to control the delivering of the liquid medicine.
12. embedded type devices according to claim 1, further include to be located between the mixing chamber and the conduit Medial compartment.
CN201280067186.1A 2011-11-22 2012-11-20 Implantable solid liquid preparation delivery apparatus, preparation and application method Expired - Fee Related CN104334226B (en)

Applications Claiming Priority (3)

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US201161629666P 2011-11-22 2011-11-22
US61/629,666 2011-11-22
PCT/US2012/066161 WO2013078257A2 (en) 2011-11-22 2012-11-20 Implantable solid-liquig drug delivery apparatus, formulations, and methods of use

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Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9610398B2 (en) 2011-11-22 2017-04-04 Incube Labs, Llc Implantable solid-liquid drug delivery apparatus, formulations, and methods of use
CN104740752A (en) * 2015-04-08 2015-07-01 四川大学华西第二医院 Implantable intelligent in-vivo drug use control device
CN104740753A (en) * 2015-04-08 2015-07-01 四川大学华西第二医院 In-vivo medicine dosing device having controllable flux
US10525247B2 (en) * 2015-08-13 2020-01-07 Medtronic, Inc. Leak reduction during implantable infusion device refill
US10939865B2 (en) 2015-10-06 2021-03-09 Ligalli B.V. Vaginal drug delivery device and vaginal diagnostic device
EP3153137A1 (en) * 2015-10-06 2017-04-12 Li Galli B.V. Vaginal drug delivery device and vaginal diagnostic device
CN105617489B (en) * 2015-12-22 2018-12-18 宋振玉 A kind of multifunctional tumor medicine injecting device
EP3338835A1 (en) 2016-12-23 2018-06-27 Sanofi-Aventis Deutschland GmbH Medicament delivery device
US10814062B2 (en) * 2017-08-31 2020-10-27 Becton, Dickinson And Company Reservoir with low volume sensor
CN115463286A (en) * 2018-01-02 2022-12-13 贝克顿·迪金森公司 Port interface for a drug delivery device
CN108837298B (en) * 2018-06-21 2020-05-22 浙江大学 Subcutaneous medicine sustained-release devices
DE102020106515A1 (en) * 2020-03-10 2021-09-16 Tricumed Medizintechnik Gmbh Implantable infusion system for infusing a liquid
EP3881875A1 (en) * 2020-03-20 2021-09-22 Littringer, Eva Delivery device for delivering a drug
WO2021222274A1 (en) * 2020-04-27 2021-11-04 Cornell University An automated controlled release device for livestock management and methods of use thereof
CN114652917B (en) * 2020-12-22 2023-12-26 北京安诺流控科技有限公司 Implantable infusion pump
US20220257854A1 (en) * 2021-02-12 2022-08-18 Medtronic, Inc. Implantable microsphere reservoir
CN116099079B (en) * 2023-03-31 2023-11-21 常州瑞神安医疗器械有限公司 Implanted medicine infusion pump

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4457752A (en) * 1982-09-13 1984-07-03 Csaba Vadasz Surgically implantable pump
US5176641A (en) 1991-07-08 1993-01-05 Infusaid, Inc. Implantable drug infusion reservoir having fluid impelling resilient foam member
US5281197A (en) * 1992-07-27 1994-01-25 Symbiosis Corporation Endoscopic hemostatic agent delivery system
US5871478A (en) * 1993-08-11 1999-02-16 Berrigan; Thomas John Implantable drug delivery means
US5690682A (en) * 1996-06-17 1997-11-25 Pharmatarget, Inc. Device and method for treatment of cardiac arrhythmia
ITFI960154A1 (en) 1996-06-27 1997-12-29 Giglio Mauro Del METHOD AND SYSTEM FOR THERAPY OF ATRIAL HYPERKINETIC ARRHYTHMIA
US6458118B1 (en) * 2000-02-23 2002-10-01 Medtronic, Inc. Drug delivery through microencapsulation
US7201746B2 (en) * 2001-04-10 2007-04-10 Medtronic, Inc. Implantable therapeutic substance delivery device having a piston pump with an anti-cavitation valve
US20030171738A1 (en) 2002-03-06 2003-09-11 Konieczynski David D. Convection-enhanced drug delivery device and method of use
US20080213331A1 (en) 2002-04-08 2008-09-04 Ardian, Inc. Methods and devices for renal nerve blocking
EP1718359B1 (en) 2004-02-10 2011-11-23 Synecor, LLC Intravascular delivery system for therapeutic agents
CN101035593B (en) 2004-07-28 2011-05-25 阿迪安公司 Methods and devices for renal nerve blocking
EP2210632B1 (en) * 2005-11-02 2012-01-18 Injectica AG Implantable infusion device with advanceable and retractable needle
US8348909B2 (en) 2006-04-28 2013-01-08 Medtronic, Inc. Implantable therapeutic substance delivery device with septum guide and method of use
US7803148B2 (en) * 2006-06-09 2010-09-28 Neurosystec Corporation Flow-induced delivery from a drug mass
EP3138603A1 (en) 2009-03-20 2017-03-08 Incube Labs, Llc Solid drug delivery apparatus, formulations and methods of use
US9610398B2 (en) 2011-11-22 2017-04-04 Incube Labs, Llc Implantable solid-liquid drug delivery apparatus, formulations, and methods of use

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AU2017202439B2 (en) 2019-04-11
US20170173258A1 (en) 2017-06-22
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AU2012340752B2 (en) 2017-01-12
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US10758668B2 (en) 2020-09-01
AU2017202439A1 (en) 2017-05-04
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AU2012340752A1 (en) 2014-06-19

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